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Blood eosinophils vary over time in relation to exacerbation and asthma control

medwireNews: Analysis of the COBRA cohort of adult patients with asthma provides insights into the role eosinophil count plays as a biomarker for predicting exacerbations and treatment efficacy.

Of 1080 patients, from 12 French academic institutions, recruited into COBRA (COhort of BRonchial obstruction and Asthma) between 2007 and 2015, 613 (57%) had severe asthma (Global Initiative for Asthma [GINA] steps 4 and 5).

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Analyses conducted at a baseline and every 6 months confirmed these patients had characteristics similar to those commonly reported for patients with severe disease.

These included poorer lung function, a higher rate of persistent airflow obstruction, and a greater likelihood of having had a severe exacerbation in the past year than the 401 patients with milder asthma (GINA steps 1–3; all p<0.0001). In addition patients with severe disease had experienced more hospitalizations and emergency department visits in the past 12 months and intensive care unit admissions during a patient’s lifetime (p<0.0001 overall).

Michel Aubier (Inserm UMR1152, Paris, France) and fellow researchers note that patients with severe asthma were taking higher doses of inhaled corticosteroids than those with milder asthma, and a respective 61.3% to75.1% versus 7.5% to 27.9% had unacceptable asthma control (p<0.0001).

The team confirmed an association between high eosinophil account and severe asthma, finding that 69.8% of patients with counts above 300 mm3 had severe asthma at baseline. And in addition, they report that, among a subset of 427 patients, eosinophil count was found to be unstable over time. Indeed, counts remained stable over 2 years of follow-up for just 32.2% of patients with counts below 150 eosinophils/mm3 (low eosinophilia), 22.9% of those with 150–300 eosinophils/mm3 (mild eosinophilia), and 24.8% of those with counts above 300 eosinophils/mm3 (high eosinophilia).

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This finding has “important clinical impact as blood eosinophils have been proposed as a biological biomarker to personalize immunological biotherapies and to target severe asthma with elevated blood eosinophils for treatment with anti-interleukin -5 (anti-IL-5) antibodies,” the researchers comment in the European Respiratory Journal.

They note that patients with a low eosinophil count at baseline were more likely to have stable eosinophilia if they had mild or moderate asthma rather than severe asthma. The opposite was true for patients with high eosinophilia counts, among whom 70% of those with severe asthma had stable eosinophilia, compared with 60% of those with milder disease and low/mild eosinophilia at baseline.

“This suggests that an eosinophil cut-off of 300 mm–3 is a more reliable biomarker than a lower one to guide the prescription of an anti-IL-5 monoclonal antibody in patients with severe asthma (GINA 5),” say Aubier and colleagues.

“It should be noted that the rate of patients with severe asthma in the COBRA cohort who shifted from GINA 4–5 to GINA 1–3 after 12 months follow-up was low, amounting to 16%,” they add.

A high eosinophil count was also associated with a higher number of exacerbations. And an increase of 200 eosinophils over time increased the rate of exacerbation before the next visit by 15% (p=0.02) and the Juniper score by 0.36 points (p=0.03), after accounting for tobacco smoking, forced expiratory volume in 1 second, long-term corticosteroid use, and anti-IgE use.

In a small subset of 54 patients with severe asthma who were taking oral corticosteroids on a daily basis throughout the study, a decrease in eosinophils correlated significantly with treatment dose (p=0.04).

“This finding underlines the importance of considering a treatment and the dose of [oral corticosteroids] when using blood eosinophil count as a biomarker to prescribe a biotherapy, such as an anti-IL-5,” the researchers stress.